Two codes of RNA editing by deamination in human diseases

RNA editing is a post-transcriptional modification that expands transcriptomic and proteomic diversity. Advances in high-throughput sequencing across a broad range of biological and pathological contexts have enabled systematic identification of editing events driven by two major RNA deaminase families: ADAR and APOBEC, which catalyze adenosine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) substitution, respectively. Genome-wide profiling of RNA editing has uncovered a substantial number of differentially edited loci in various conditions, implicating the post-transcriptional events in physiological and pathological regulation. Aberrant RNA editing alters the functional information of coding and noncoding transcripts, perturbing protein activity, RNA stability and other gene expression programs, which contributes to immune imbalance, viral infection, neurological impairment, metabolic disorders and tumorigenesis. The two codes of A-to-I and C-to-U RNA editing harbor common potential for single base conversion with varied expression of responsible enzymes across many physiological and pathological conditions. Here we provide a comprehensive and parallel overview on ADAR-mediated A-to-I and APOBEC-mediated C-to-U editing, with emphasis on their molecular mechanisms, physiological roles and pathological dysregulation in human health and disease.